This research proposal is a revised R01 application in response to the Program Announcement "Continued Development and Maintenance of Bioinformatics and Computational Biology Software" for five years of funding to continue development and maintenance of an existing software package for analysis of magnetic resonance images of the brain of premature and fullterm newborn infants. A significant need exists for continued development of our existing package of MRI analysis tools for this age range as no alternative software packages are currently available or suitable for this age range. The research proposed here involves the enhancement of an existing software package for quantitative analysis of MRI of the developing brain by the implementation, as open-source software, of existing validated and proven algorithms, and the creation of a user-friendly graphical user interface to enable end users to easily apply these methods. The objective is to enhance the existing software to create a platform for scientific discovery and for clinical research. This is a challenging task because the developing newborn brain poses unique challenges not apparent in older subjects, including significant age-dependent contrast properties of brain tissue, rapid microstructural and macrostructural changes, and spatial resolution of features of interest close to the limit of imaging resolution. Addressing these challenges satisfactorily requires the unique expertise and methods and techniques we have developed over the past ten years and which are currently not available elsewhere. Impact: The research team has significant nationally and internationally unique collaborative experience in the acquisition of images of the newborn infant brain, pioneering expertise in the development and application of post-acquisition image processing to this population, and an extensive track record in the interpretation of the nature of alterations of cerebral structure in the newborn infant brain. This software currently has a significant user community who will immediately benefit from the enhancements. Furthermore, creating a supported open source software package will enable the broader community of scientists and clinicians dealing with pediatric brain development, who are currently not served by any existing software, to adopt and utilize the package, and will have a significant long-term impact in the domain of pediatric neuroimaging studies. [unreadable] [unreadable] [unreadable]